1. Field of the Invention
The present invention relates to gels and mixed gels of hyaluronic acid (HA), formulations containing them and methods for preparing them.
2. The Prior Art
Hyaluronic acid is a well known, naturally occurring polysaccharide containing alternating N-acetyl-D-glucosamine and D-glucuronic acid monosaccharide units linked with .beta.1.fwdarw.4 bonds and the disaccharide units linked with .beta.1.fwdarw.3 glycoside bonds. Hyaluronic acid usually occurs as the sodium salt. The molecular weight of HA is generally within the range of 50,000 up to 8.times.10.sup.6 and even higher.
The prior art describes the cross-linking of HA with the use of 1,2,3,4-diepoxybutane in alkaline medium at 50.degree. C. (T. C. Laurent, K. Hellsing, and B. Gelotte, Acta Chem. Scand. 18 [1984], No 1, 274-5). The product obtained by that method is a gel which substantially swells in water.
It is also known that divinyl sulfone (DVS) is used for cross-linking polysaccharides, especially cellulose (U.S. Pat. No. 3,357,784).